86 research outputs found

    Radial growth responses of upland oaks following recurrent restoration treatments in northern Mississippi

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    Fire exclusion over the past century has substantially altered composition, structure, and fuel dynamics in upland oak-hickory (Quercus-Carya) forests in the Southeastern United States. Numerous restoration efforts have been made to re-establish historical disturbance regimes into these altered forests. However, our understanding of the implications of restorative disturbances on stand dynamics has primarily been limited to shifts in species composition and post-disturbance regeneration. Therefore, we examined annual radial growth responses of dominant upland oaks following a combination of prescribed fires (2004, 2006, 2008, 2010, 2012, and 2014) and thinning (starting in 2004) treatments (thin+burn) in stands which had previously been unburned since the early 1900s. Radial stem growth rates were quantified using tree cores from 22 post oak (Q. stellata) and southern red oak (Q. falcata) in a 2.5-acre thin+burn and control stand at the Strawberry Plains Audubon Center in northern Mississippi. Radial growth rates were not significantly greater following repeated thinning and prescribed burning than prior to treatment initiation for either post oak or southern red oak. For the first 6 years after the initial thin, the annual ring width for southern red oak was identical in the thin+burn (1.9 ± 0.1 mm year-1) and control (2.0 ± 0.2 mm year-1) stands. However, in 2010 radial growth for southern red oak in the thin+burn increased such that the annual ring width for 2010 was 22 percent greater in the thin+burn than in the control stands. In contrast to the positive growth response in southern red oak (2 percent), post oak demonstrated a significantly different (p = 0.014) negative response (-19 percent) in the relative percent change in total radial growth for the 11-year period post-treatment initiation when compared to the 11-year period prior to treatment initiation. Radial growth for both species was negatively impacted by a severe drought in 2007 with southern red oak exhibiting the greatest decrease in radial growth. Results from this study highlight the underlying role of climatic factors and species life history characteristics in evaluating radial growth patterns following forest disturbances

    Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome

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    The cardiac action potential is critical to the production of a synchronized heartbeat. This electrical impulse is governed by the intricate activity of cardiac ion channels, among them the cardiac voltage-gated potassium (Kv) channels KCNQ1 and hERG as well as the voltage-gated sodium (Nav) channel encoded by SCN5A. Each channel performs a highly distinct function, despite sharing a common topology and structural components. These three channels are also the primary proteins mutated in congenital long QT syndrome (LQTS), a genetic condition that predisposes to cardiac arrhythmia and sudden cardiac death due to impaired repolarization of the action potential and has a particular proclivity for reentrant ventricular arrhythmias. Recent cryo-electron microscopy structures of human KCNQ1 and hERG, along with the rat homolog of SCN5A and other mammalian sodium channels, provide atomic-level insight into the structure and function of these proteins that advance our understanding of their distinct functions in the cardiac action potential, as well as the molecular basis of LQTS. In this review, the gating, regulation, LQTS mechanisms, and pharmacological properties of KCNQ1, hERG, and SCN5A are discussed in light of these recent structural findings

    Association of Race Consciousness With the Patient- Physician Relationship, Medication Adherence, and Blood Pressure in Urban Primary Care Patients

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    background Race consciousness (the frequency with which one thinks about his or her own race) is a measure that may be useful in assessing whether racial discrimination negatively impacts blood pressure (BP). However, the relation between race consciousness and BP has yet to be empirically tested, especially within the context of the patient-physician relationship and medication adherence

    A comparative genomics screen identifies a Sinorhizobium meliloti 1021 sodM-like gene strongly expressed within host plant nodules

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    Background We have used the genomic data in the Integrated Microbial Genomes system of the Department of Energy’s Joint Genome Institute to make predictions about rhizobial open reading frames that play a role in nodulation of host plants. The genomic data was screened by searching for ORFs conserved in α-proteobacterial rhizobia, but not conserved in closely-related non-nitrogen-fixing α-proteobacteria. Results Using this approach, we identified many genes known to be involved in nodulation or nitrogen fixation, as well as several new candidate genes. We knocked out selected new genes and assayed for the presence of nodulation phenotypes and/or nodule-specific expression. One of these genes, SMc00911, is strongly expressed by bacterial cells within host plant nodules, but is expressed minimally by free-living bacterial cells. A strain carrying an insertion mutation in SMc00911 is not defective in the symbiosis with host plants, but in contrast to expectations, this mutant strain is able to out-compete the S. meliloti 1021 wild type strain for nodule occupancy in co-inoculation experiments. The SMc00911 ORF is predicted to encode a “SodM-like” (superoxide dismutase-like) protein containing a rhodanese sulfurtransferase domain at the N-terminus and a chromate-resistance superfamily domain at the C-terminus. Several other ORFs (SMb20360, SMc01562, SMc01266, SMc03964, and the SMc01424-22 operon) identified in the screen are expressed at a moderate level by bacteria within nodules, but not by free-living bacteria. Conclusions Based on the analysis of ORFs identified in this study, we conclude that this comparative genomics approach can identify rhizobial genes involved in the nitrogen-fixing symbiosis with host plants, although none of the newly identified genes were found to be essential for this process

    Structural Mechanism of Laforin Function in Glycogen Dephosphorylation and Lafora Disease

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    Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated tertiary and quaternary structure. Structure-guided mutagenesis combined with biophysical and biochemical analyses reveal the basis for normal function of laforin in glycogen metabolism. Analyses of LD patient mutations define the mechanism by which subsets of mutations disrupt laforin function. These data provide fundamental insights connecting glycogen metabolism to neurodegenerative disease

    An empirical pipeline for personalized diagnosis of Lafora disease mutations

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    22 páginas, 6 figuras, 2 tablas. Contiene material suplementarioLafora disease (LD) is a fatal childhood dementia characterized by progressive myoclonic epilepsy manifesting in the teenage years, rapid neurological decline, and death typically within ten years of onset. Mutations in either EPM2A, encoding the glycogen phosphatase laforin, or EPM2B, encoding the E3 ligase malin, cause LD. Whole exome sequencing has revealed many EPM2A variants associated with late-onset or slower disease progression. We established an empirical pipeline for characterizing the functional consequences of laforin missense mutations in vitro using complementary biochemical approaches. Analysis of 26 mutations revealed distinct functional classes associated with different outcomes that were supported by clinical cases. For example, F321C and G279C mutations have attenuated functional defects and are associated with slow progression. This pipeline enabled rapid characterization and classification of newly identified EPM2A mutations, providing clinicians and researchers genetic information to guide treatment of LD patients.This work was supported by the National Institutes of Health (P01 NS097197 to M.S.G., J.M.S. and P.S., R35 NS116824 to M.S.G., and F31 NS093892 to M.K.B), National Science Foundation (DBI2018007 and MCB1817414 to M.S.G.), and Epilepsy Foundation New Therapy Commercialization Grant to M.S.G. M.K.B. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (No. 754510M). This project also received funding from the Spanish Ministry of Science and Innovation (SAF2017-83151-R to P.S. and RTI2018-095784b-100SAF to J.M.S).Peer reviewe

    Measurement of Contractile Stress Generated by Cultured Rat Muscle on Silicon Cantilevers for Toxin Detection and Muscle Performance Enhancement

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    Background: To date, biological components have been incorporated into MEMS devices to create cell-based sensors and assays, motors and actuators, and pumps. Bio-MEMS technologies present a unique opportunity to study fundamental biological processes at a level unrealized with previous methods. The capability to miniaturize analytical systems enables researchers to perform multiple experiments in parallel and with a high degree of control over experimental variables for high-content screening applications.Methodology/Principal Findings: We have demonstrated a biological microelectromechanical system (BioMEMS) based on silicon cantilevers and an AFM detection system for studying the physiology and kinetics of myotubes derived from embryonic rat skeletal muscle. It was shown that it is possible to interrogate and observe muscle behavior in real time, as well as selectively stimulate the contraction of myotubes with the device. Stress generation of the tissue was estimated using a modification of Stoney's equation. Calculated stress values were in excellent agreement with previously published results for cultured myotubes, but not adult skeletal muscle. Other parameters such as time to peak tension (TPT), the time to half relaxation (KRT) were compared to the literature. It was observed that the myotubes grown on the BioMEMS device, while generating stress magnitudes comparable to those previously published, exhibited slower TPT and KRT values. However, growth in an enhanced media increased these values. From these data it was concluded that the myotubes cultured on the cantilevers were of an embryonic phenotype. The system was also shown to be responsive to the application of a toxin, veratridine.Conclusions/Significance: The device demonstrated here will provide a useful foundation for studying various aspects of muscle physiology and behavior in a controlled high-throughput manner as well as be useful for biosensor and drug discovery applications

    The `Parahippocampal Place Area' Responds Selectively to High Spatial Frequencies

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    Defining the exact mechanisms by which the brain processes visual objects and scenes remains an unresolved challenge. Valuable clues to this process have emerged from the demonstration that clusters of neurons (“modules”) in inferior temporal cortex apparently respond selectively to specific categories of visual stimuli, such as places/scenes. However, the higher-order “category-selective” response could also reflect specific lower-level spatial factors. Here we tested this idea in multiple functional MRI experiments, in humans and macaque monkeys, by systematically manipulating the spatial content of geometrical shapes and natural images. These tests revealed that visual spatial discontinuities (as reflected by an increased response to high spatial frequencies) selectively activate a well-known place-selective region of visual cortex (the “parahippocampal place area”) in humans. In macaques, we demonstrate a homologous cortical area, and show that it also responds selectively to higher spatial frequencies. The parahippocampal place area may use such information for detecting object borders and scene details during spatial perception and navigation.National Institutes of Health (U.S.) (NIH Grant R01 MH6752)National Institutes of Health (U.S.) (grant R01 EY017081)Athinoula A. Martinos Center for Biomedical ImagingNational Center for Research Resources (U.S.)Mind Research Institut

    Identifying Contributions to the Stellar Halo from Accreted, Kicked-Out, and In Situ Populations

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    [Abridged] We present a medium-resolution spectroscopic survey of late-type giant stars at mid-Galactic latitudes of (30<b<60^{\circ}<|b|<60^{\circ}), designed to probe the properties of this population to distances of \sim9 kpc. Because M giants are generally metal-rich and we have limited contamination from thin disk stars by the latitude selection, most of the stars in the survey are expected to be members of the thick disk (\sim-0.6) with some contribution from the metal-rich component of the nearby halo. Here we report first results for 1799 stars. The distribution of radial velocity (RV) as a function of l for these stars shows (1) the expected thick disk population and (2) local metal-rich halo stars moving at high speeds relative to the disk, that in some cases form distinct sequences in RV-ll space. High-resolution echelle spectra taken for 34 of these "RV outliers" reveal the following patterns across the [Ti/Fe]-[Fe/H] plane: seventeen of the stars have abundances reminiscent of the populations present in dwarf satellites of the Milky Way; eight have abundances coincident with those of the Galactic disk and more metal-rich halo; and nine of the stars fall on the locus defined by the majority of stars in the halo. The chemical abundance trends of the RV outliers suggest that this sample consists predominantly of stars accreted from infalling dwarf galaxies. A smaller fraction of stars in the RV outlier sample may have been formed in the inner Galaxy and subsequently kicked to higher eccentricity orbits, but the sample is not large enough to distinguish conclusively between this interpretation and the alternative that these stars represent the tail of the velocity distribution of the thick disk. Our data do not rule out the possibility that a minority of the sample could have formed from gas {\it in situ} on their current orbits.Comment: 43 pages, 9 figures, 4 tables, published in the Astrophysical Journa

    Study of Women, Infant feeding, and Type 2 diabetes mellitus after GDM pregnancy (SWIFT), a prospective cohort study: methodology and design

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    <p>Abstract</p> <p>Background</p> <p>Women with history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes within 5 years after delivery. Evidence that lactation duration influences incident type 2 diabetes after GDM pregnancy is based on one retrospective study reporting a null association. The Study of Women, Infant Feeding and Type 2 Diabetes after GDM pregnancy (SWIFT) is a prospective cohort study of postpartum women with recent GDM within the Kaiser Permanente Northern California (KPNC) integrated health care system. The primary goal of SWIFT is to assess whether prolonged, intensive lactation as compared to formula feeding reduces the 2-year incidence of type 2 diabetes mellitus among women with GDM. The study also examines whether lactation intensity and duration have persistent favorable effects on blood glucose, insulin resistance, and adiposity during the 2-year postpartum period. This report describes the design and methods implemented for this study to obtain the clinical, biochemical, anthropometric, and behavioral measurements during the recruitment and follow-up phases.</p> <p>Methods</p> <p>SWIFT is a prospective, observational cohort study enrolling and following over 1, 000 postpartum women diagnosed with GDM during pregnancy within KPNC. The study enrolled women at 6-9 weeks postpartum (baseline) who had been diagnosed by standard GDM criteria, aged 20-45 years, delivered a singleton, term (greater than or equal to 35 weeks gestation) live birth, were not using medications affecting glucose tolerance, and not planning another pregnancy or moving out of the area within the next 2 years. Participants who are free of type 2 diabetes and other serious medical conditions at baseline are screened for type 2 diabetes annually within the first 2 years after delivery. Recruitment began in September 2008 and ends in December 2011. Data are being collected through pregnancy and early postpartum telephone interviews, self-administered monthly mailed questionnaires (3-11 months postpartum), a telephone interview at 6 months, and annual in-person examinations at which a 75 g 2-hour OGTT is conducted, anthropometric measurements are obtained, and self- and interviewer-administered questionnaires are completed.</p> <p>Discussion</p> <p>This is the first, large prospective, community-based study involving a racially and ethnically diverse cohort of women with recent GDM that rigorously assesses lactation intensity and duration and examines their relationship to incident type 2 diabetes while accounting for numerous potential confounders not assessed previously.</p
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